THE CHARACTERIZATION OF IMMUNOREGULATORY FACTOR-MEDIATED GROWTH AND DIFFERENTIATION OF LEUKEMIC B CELLS ISOLATED FROM PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA.
Item
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Title
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THE CHARACTERIZATION OF IMMUNOREGULATORY FACTOR-MEDIATED GROWTH AND DIFFERENTIATION OF LEUKEMIC B CELLS ISOLATED FROM PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA.
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Identifier
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AAI8713802
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identifier
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8713802
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Creator
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STEINBERG, JOSEPH.
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Contributor
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Constantin A . Bona
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Date
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1987
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, General
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Abstract
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The loss of systemic immunocompetence which arises as a frequent manifestation of chronic lymphocytic leukemia (CLL) is viewed here, in part, as a consequence of binding and sequestration of essential soluble immunoregulatory factors by circulating monoclonal B lymphocytes of leukemic origin. Indirect evidence for this contention is furnished through an in vitro functional analysis of isolated neoplastic B cells from a group of 20 patients. Individual essentially pure E rosette-negative largely leukemic B cell lines exhibited highly varible proliferative and differentiative responses when cultured with conditioned medium (CM) prepared from PHA-P stimulated normal peripheral blood mononuclear cells. All cell lines exhibited some degree of proliferation in four-day old cultures with CM and the B cell polyclonal activator rabbit antihuman antibody (anti-{dollar}\mu{dollar}). In addition, of the leukemic lines tested, the most ontologically mature populations as judged by surface immunofluorescence could also be induced to secrete significant quantities of immunoglobulin (Ig) when cultured for six days in the presence of CM alone. Standard concentrations (10 {dollar}\mu{dollar}g/ml) of F(ab{dollar}\sp\prime)\sb 2{dollar} fragments of anti-{dollar}\mu{dollar} were not stimulatory in every case but instead were able to block or induce growth of several spontaneously proliferating B cell lines in a dose-dependent manner. Costimulation with CM plus anti-{dollar}\mu{dollar} to a large degree helped alleviate the proliferation inhibition. The response of leukemic cells to the commonly utilized polyclonal activators Staphylococcus aureus Cowan I strain (SAC) and to the phorbol ester TPA alone or in combination with CM was also investigated. The majority of CLL lines tested, unlike normal polyclonal B cells, were not proliferatively responsive to SAC. TPA added at the initiation of cultures was usually found to effectively synergize with CM; however, in several cases where cells were cultured with CM plus anti-{dollar}\mu{dollar}, the use of TPA actually reduced the level of proliferation. In addition, when utilized to optimize proliferation in preparation for karyotypic analysis, TPA produced mitotic figures of insufficient quality containing chromosomes which were poorly dispersed and highly contracted. By comparison, recombinant IL-2 in parallel experiments when substituted for TPA yielded higher quality mitotic figures indicating that the suboptimal mitotic effects were TPA-specific. (Abstract shortened with permission of author.).
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biology
